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At least 217 records · Page 12Linked to original sources
PubMed1977

Pharmacokinetics and relative bioavailability of levomepromazine after repeated administration of tablets and syrup.

Plasma levels of levomepromazine and its sulphoxide were measured in 8 psychiatric patients after repeated doses of levomepromazine tablets or syrup. The rate and extent of absorption of the drug were similar for the two dosage forms, although the extent of presystemic metabolism appeared to be slightly greater after administration of syrup than of tablets. The biological half-life of levomepromazine ranged from 16.5 h to 77.8 h, and a 13-fold variation was seen in the ratio of the total clearance to the absorbed fraction of the dose (Cl/Fpo). It is postulated that individual variation in the dose required for therapy was due in part to individual variation in the pharmacokinetics of the drug.

Administration, Oral↗
PubMed1986

Importance of oxidative polymorphism and levomepromazine treatment on the steady-state blood concentrations of clomipramine and its major metabolites.

The relationship between the debrisoquine oxidation status and the metabolism of clomipramine was studied in nine healthy volunteers (five rapid hydroxylators, three slow hydroxylators and one of intermediate status). The hydroxylation of clomipramine and demethylclomipramine were found to covary with that of debrisoquine, whereas demethylation of clomipramine seemed to be independent of the debrisoquine hydroxylation phenotype. The steady-state blood concentrations of clomipramine and its three main metabolites were measured in 122 depressed patients. Thirteen patients who concomitantly received a neuroleptic tended to have higher levels of demethylclomipramine and clomipramine, whereas the levels of the hydroxylated metabolites were hardly affected. Benzodiazepine co-administration did not modify the pharmacokinetics of clomipramine. The results suggest that benzodiazepines rather than levomepromazine should be used in depressed patients with anxiety and/or agitation in combination with the antidepressant treatment.

Adult↗
PubMed1992

Alopecia and mood stabilizers: two case reports.

Two cases of alopecia observed during treatment with lithium and valproate are described, and the recent literature on this subject is reviewed. Our clinical observations confirm earlier reports. These toxic alopecias are characterized by a diffuse but rarely total hair loss. After stopping medication, the hair grows back generally and completely. Two cases of toxic alopecia are presented where hair grew back following a substitution of lithium by valproate in the first case and after stopping valproate in the second. The evaluation and therapeutic attitude in the presence of alopecia in patients needing mood stabilizers are also discussed.

Adult↗
PubMedDate not supplied

Metabolism of levomepromazine in man.

The phenothiazine drug, levomepromazine (LM), is used in the treatment of psychiatric disorders and as an analgesic. A single 50 or 100 mg dose of LM was given to healthy male volunteers, and urine samples were collected for 24 h. The urine was treated with beta-glucuronidase, purified by solid-phase extraction, and analyzed on a GC-MS system for identification of LM metabolites. Mass spectra suggesting 14 different LM metabolites were obtained from the samples. Our of these, 13 spectra could be ascribed to specific metabolites, 5 of which have not previously been identified. All these 5 metabolites were hydroxylated at the phenothiazine nucleus. Although the applied method did not determine the positions of hydroxyl groups on phenothiazine nuclei. 3 of the 5 metabolites were identified as O-desmethyl 3-hydroxy LM, O-desmethyl 7-hydroxy LM, and N,O-didesmethyl 7-hydroxy LM, based on their chromatographic properties. In addition two metabolites, one being hydroxylated on the phenothiazine nucleus, and one being O-demethylated and hydroxylated on the nucleus, were found. It is suggested that these were 8-hydroxy LM and O-desmethyl 8-hydroxy LM. The concentrations of 3-hydroxy LM (free+conjugated) appeared to be much higher than the concentrations of any other metabolite in the samples.

Antipsychotic Agents↗
PubMed2006

Neuroleptic drugs in the human brain: clinical impact of persistence and region-specific distribution.

After discontinuation of neuroleptic agents, their effects are still present for a long time. The exact underlaying mechanisms are still unclear. In two previous studies we measured the concentrations and region-specific distribution of haloperidol (Kornhuber et al. 1999) and levomepromazine (Kornhuber et al. 2006) in postmortem human brain tissues. The aim of the present paper is to compare the results of these two studies. Even after short-term treatment, haloperidol and levomepromazine concentrations reach high levels in human brain tissue. Haloperidol concentrations in brain tissue are 10-30 times higher than the optimum serum concentrations in the treatment of schizophrenia. The brain-to-blood concentration ratio of levomepromazine is about 10. The estimated elimination half-life of these drugs in brain tissue are 6.8 days (haloperidol), 7.9 days (levomepromazine) and 27.8 days for the metabolite desmethyl-levomepromazine, respectively. After two half-lives (about 2 weeks), a considerable amount of drug remains in brain tissue. Haloperidol concentrations appeared to be homogeneously distributed across different brain areas, whereas levomepromazine shows a region-specific distribution, with highest values in the basal ganglia. The persistence of neuroleptic drugs in the human brain might explain their prolonged effects and side effects. The region-specific distribution of levomepromazine may increase our understanding of both the preferential toxicity of neuroleptic drugs against basal ganglia structures and higher basal ganglia volumes in patients treated with neuroleptics.

Aged↗
PubMed2005

Region specific distribution of levomepromazine in the human brain.

OBJECTIVE: The aim of this study was to examine concentrations of levomepromazine and its metabolite desmethyl-levomepromazine in different regions of human brain and in relationship to drug-free time. METHODS: Drug concentrations were measured in up to 43 regions of 5 postmortem human brains of patients previously treated with levomepromazine. To enable statistical comparison across brain regions several smaller brain areas were put together to form larger brain areas (cortex cerebri, limbic system, cerebellum, basal ganglia, thalamus). Mean values of drug concentrations in these larger brain areas were used in a repeated measurement ANOVA to analyze for region specific distribution. The elimination half-life in brain tissue was estimated with a NONMEM population kinetic analysis using the mean value of all brain regions of an individual case. RESULTS: Levomepromazine and desmethyl-levomepromazine appear to accumulate in human brain tissue relative to blood. Mean concentrations differed largely between individual brains, in part due to differences in dose of drug, duration of treatment and drug-free time before death. There was an apparent region-specific difference in levomepromazine concentrations with highest values in the basal ganglia (mean 316 ng/g) and lowest values in the cortex cerebri (mean 209 ng/g). The elimination half-life from brain tissue is longer than from blood and was calculated to be about one week. Similar results were obtained with desmethyl-levomepromazine. CONCLUSIONS: Levomepromazine shows a region-specific distribution in the human brain with highest values in the basal ganglia. This might be the consequence of low expression of the metabolic enzyme Cyp2D6 in the basal ganglia. If this finding is true also for other neuroleptic drugs it might increase our understanding of preferential toxicity of neuroleptic drugs against basal ganglia structures and higher volumes of basal ganglia of neuroleptic-treated patients. Furthermore, patients exposed to levomepromazine cannot be considered to be free of residual effects of the drug for a number of weeks after withdrawal.

Aged↗